willkommen in - Saint Louis University

FACULTy
vieW In 2002 I was invited to join AAHRPP’s
by Jesse A. goldner
John D. Valentine
Professor of Law
Jesse A. Goldner holds
secondary appointments in the
Departments of Psychiatry and
Pediatrics at the University’s
School of Medicine as well
as in both its School of Public
Health and the Center for Health
Care Ethics. Together with
three co-authors, in 2005 he
published Ethics and Regulation
of Research with Human
Subjects (Lexis). In addition to
his work with AAHRPP, in the
fall of 2005 he was appointed
to the 19 person Accreditation
Committee of the American Bar
Association’s Section on Legal
Education and Admissions to the
Bar, which is responsible for the
accreditation of law schools in
the United States.
Reducing the Perils of
Participating in Research
on Human Subjects
Nicole Wan was a 19-year-old freshman at the
University of Rochester in 1996. Ellen Roche
was a 24-year-old laboratory technician at Johns
Hopkins University’s Asthma and Allergy Center
in 2001. Jesse Gelsinger was an 18-year-old who
lived in Arizona in 1999. What the three had in
common was that each participated in a clinical
research study. Each died as a result.
Wan and Roche were “healthy
volunteers.” Gelsinger suffered from Ornithine
Transcarbamylase Deficiency, a genetic disorder
that causes excessive amounts of ammonia to
appear in the blood. While without treatment the
disorder can lead to behavioral disorders, mental
retardation, coma or even death, Gelsinger had
been doing well on his then current medication
regime. The study was a “leading edge” gene
transfer investigation, conducted at the University
of Pennsylvania, that the researchers thought
might ameliorate the condition. Though some
federal regulations mandate review of many
proposed studies such as these, little monitoring
occurs regarding how those reviews are conducted.
Investigations after the deaths in each situation
concluded that appropriate guidelines for the
conduct of the research had not been followed at
the institutions.
In 1965 leading veterinarians and
researchers organized what is now known as
the American Association for Accreditation
of Laboratory Animal Care International, as
a private, nonprofit organization. Over the
last 41 years it has accredited more than 670
operations worldwide (including organizations
such as Saint Louis University, Stanford
University, the National Institutes of Health and
GlaxoSmithKline pharmaceuticals), elevating the
standard for research laboratory animal care to
new levels. Rather strangely (and cynically, some
might observe), it was only a mere five years ago
that a similar organization, the Association for
the Accreditation of Human Research Protection
Programs, Inc. (AAHRPP) was created to offer a
comparable program to institutions that conduct
or review biomedical, social and behavioral
science research in which human beings serve as
research subjects.
AAHRPP was established by seven founding
organizations, including groups such as the
Association of American Medical Colleges, the
American Association of Universities and the
National Association of State Universities and
Land Grant Colleges. A national organization
based in Washington, D.C., it developed in
the wake of a series of disciplinary measures
against research institutions taken by various
federal agencies, such as the Food and Drug
Administration and the U.S. Department
of Health and Human Services, which are
responsible for overseeing the manner in which
such research occurs. Those actions involved
stopping or severely limiting the conduct of
research at some of the country’s leading medical
centers including, among others, Duke, Johns
Hopkins and the University of Pennsylvania after
the deaths of Wan, Roche and Gelsinger. As one
small example of the effects of the federal agencies’
actions, the annual budget for human subject
participant protection programs at Duke increased
from approximately $100,000 to over $1 million
in the course of a few months as it attempted to
meet requisite federal standards.
In response to the resulting public concern
for protecting research participants, AAHRPP was
established “not only to ensure compliance with
federal regulations, but to raise the bar in human
research protection by helping institutions reach
performance standards that surpass the threshold of
state and federal requirements.” The organization
also aims to “promote scientifically meritorious and
ethically sound research by fostering and advancing
the ethical and professional conduct of persons
and organizations that engage in research with
human participants.” AAHRPP achieves its mission
by using an accreditation process based on selfassessment,
peer review and education.
initial Council on Accreditation, which
determines the status of applicant organizations.
In 2005 I served as the Council’s first
chairperson and continue to participate by
serving as a member of the group and by
conducting site evaluation visits on its behalf.
The invitation to join the Council came about
for three reasons, each related to my work
at SLU: (1) For some eighteen years I had
been a member of (and, from 1998 through
2003, had chaired) SLU’s Institutional Review
Board (IRB). This is an interdisciplinary
group, including both scientists and nonscientists,
primarily comprised of faculty from
throughout the University, but also including
non-University-affiliated individuals. The
IRB, through a peer review process, evaluates
individual proposals to conduct research
involving human subjects by faculty, staff and
graduate students at the University. The purpose
is to ensure that ethical principles are followed,
primarily by seeing to it that investigators are
minimizing risks to research participants and
obtaining appropriate informed consent from
these subjects. (2) Much of my academic writing
in the last decade has focused on the regulation
of research. Most recently, I co-authored a law
school casebook on the subject. (3) Since 1988
I had regularly conducted site evaluations of
other American law schools for purposes of their
accreditation on behalf of the Accreditation
Committee of the American Bar Association’s
Section on Legal Education and Admissions
to the Bar. This familiarized me with the
accreditation process, albeit of a very
different type.
How does AAHRPP work? AAHRPP is not
affiliated with the government. It is institutions,
including universities, hospitals and free-standing
research facilities, that voluntarily apply to
AAHRPP for accreditation. Applicants must
complete a wide-ranging questionnaire and
submit extensive supporting materials, including
their policies and procedures, all relating to how
their institution goes about protecting the rights
of those who serve as research participants. This
is in an effort to evaluate that they meet some
twenty different standards that include seventyfive
separate elements. Among the issues explored
are the involvement of organizational leaders
and the adequacy of resources they provide
to the process. In reviewing the competency
and sophistication of the institution’s research
The purpose is to insure that
ethical principles are followed,
primarily by seeing to it that
investigators are minimizing
risks to research participants.
“
”
review units (typically the IRBs), we examine
their abilities to (a) assess risks and benefits; (b)
oversee the appropriate recruitment and selection
of subjects; (c) protect participants’ privacy and
the confidentiality of the data obtained; and
(d) monitor the process of obtaining informed
consent from participants and the content of the
information provided to them.
Another focus is that of the investigators
themselves: their familiarity with research ethics,
their abilities to follow applicable laws and
regulations and their understanding that the
protections of the rights and welfare of research
participants is their primary concern. Attention
also is paid to the nature of the contractual
relationship between the organization itself and
outside agencies such as pharmaceutical and
medical device companies that sponsor research.
This involves ensuring that there is appropriate
communication of information that might affect
the ongoing oversight of research protocols by
IRBs as well as maximizing the likelihood that
the benefits of the knowledge obtained through
research are realized and the interests of current
and future participants are protected. Finally, the
standards address how the organization responds
to concerns of research participants and engages
in outreach efforts by offering educational
opportunities to participants to enable them to
better understand research.
After the submitted materials are reviewed,
AAHRPP appoints a site evaluation team,
typically comprised of two to five members who
have training and experience in conducting
evaluations and who have no affiliations with the
applicant institution. They will spend between
two and five days at the institution, depending
on its size and number of research projects at the
institution. They then draft a lengthy and highly
detailed report describing what they encountered
at the institution, including an examination
of protocols and other records and interviews
with investigators, staff and members of the
IRB. Ultimately, these reports are reviewed by
the Council on Accreditation which determines
if the standards have been met so as to merit
accreditation. Not infrequently, institutions are
placed in an “accreditation pending” category
when the Council determines that additional
efforts need to be made by the institution. At the
present time some thirty-nine institutions have
met accreditation standards, though nearly four
hundred are “in the pipeline” and will be site
visited within the next year or two.
The process, both for institutions and
for those who conduct site evaluations and
participate in Council reviews, is an arduous
one. As critical as the development of ongoing
scholarship in this area may be, it is equally
important that those of us who spend much of
our time in the proverbial ivory tower, recognize
the need to “descend” and expend some of our
efforts in the hands-on work that may more
directly affect the ability of researchers and their
institutions to protect research participants like
Nicole Wan, Ellen Roche and Jesse Gelsinger. As
AAHRPP accreditation becomes more prevalent,
it is quite likely that the safety of research subjects
will increase and the lives and health of countless
others will benefit as well.
20 Saint Louis Brief Fall 2006 Fall 2006 Saint Louis Brief 2